Apparatus and method for implanted self-powered medication dispensing having timing and evaluator means

ABSTRACT

An apparatus for dispensing drugs and other medications within the body is adapted to be entirely implanted and to dispense such substances over a long period of time, e.g., one to several years, in accordance with the actual needs of the patient. A self-powered dispensing device stores a single or plural substances in powdered, liquid, or other dispensable form. Logic and self-timing means control dispensing by monitoring single or plural sensors implanted in the body and evaluating the sensed data in order to control both the conditions under which and the kind of dispensing which takes place.

United States Patent 1191 Ellinwood, Jr.

1451 Dec. 2, 1975 Tonbridge Way, Durham, NC. 27707 [22] Filed: Apr. 23,1974 [21] Appl. No.: 463,262

[52] U.S. Cl. 128/260; 128/2.06 A; 128/214 F; 128/218 A; 128/D1G. 1;128/D1G. 13; 128/2 R; 128/214 E [51] Int. Cl. A61M 5/00; A61M 7/00 [58]Field of Search 128/260, 2.06 A, 214 F, 128/218 A, DIG. 1, 214 E, DIG.13, 213, 2.08, 2 A, 2 R

[56] References Cited UNITED STATES PATENTS 2,690,178 9/1954 Bickford128/213 2,925,814 2/1960 Vibber et a1. 128/214 F 3,091,239 5/1963Moeller 1 128/214 F 3,527,220 9/1970 Summers 128/260 SENSOR AT SENSEDSITE TIMED MEDICATION E PERIODIC SENSING AND DATA EVALUATION CIRCUFIRY3,651,806 3/1972 Hirshberg 128/214 E 3,692,027 9/1972 Ellinwood, Jr....128/260 3,701,345 10/1972 Heilman et a1. 128/218 A 3,731,681 5/1973Blackshear et al. 128/214 F FOREIGN PATENTS OR APPLICATIONS 769,8763/1957 United Kingdom 128/214 E Primary Examiner-Aldrich F. MedberyAttorney, Agent, or FirmB. B. Olive [57] ABSTRACT An apparatus fordispensing drugs and other medications within the body is adapted to beentirely implanted and to dispense such substances over a long period oftime, e.g., one to several years, in accordance with the actual needs ofthe patient. A selfpowered dispensing device stores a single or pluralsubstances in powdered, liquid, or other dispensable form. Logic andself-timing means control dispensing by monitoring single or pluralsensors implanted in the body and evaluating the sensed data in order tocontrol both the conditions under which and the kind of dispensing whichtakes place.

20 Claims, 18 Drawing Figures IMPLANTED HOUSING SPECIAL MEDICATIONBATTERIPOWER SOURCE US. Patent Dec. 2, 1975 Sheet 1 of7 3,923,060

IMPLANTED l HOUSING SENSED SITE 30- SENSOR AT TIMED DATA EVALUATION ANDDISPENSING MEANS DECISION CONTROL CIRCUIT-RY MEDICATION STORAGE TOTREATED SITE FIG.

IMPLANTED mousme ELECTRIC POTENTIAL SENSOR J DISPENSING MEANS E G A R OT S 4 C H R mo U m II VI mm I U UC mm S C CUG mm E M WEA C S I, A H mm Um 4 N m N E D E. M

TO CARDIAC SAC OR OTHER TARGET ORGAN FIG. 2

U.S. Patent Dec. 2, 1975 Sheet 2 of7 3,923,060

I MPLANTED RRESSURE TRANSDUCER A 51 PERIODIC SENSOR TIMING I AND BLOODPRESSURE l I 52/MATCHING CIRCUITRY I 50v] MEDICATION IMPLANTED I STORAGEHOUSING FIG. 3

V TO TREATED SITE BODY CHEMISTRY SENSOR] PERIODIC SENSOR TIMING ANDTHRESHOLD DISCRIMINATION CIRCUITRY |MPLANTED/,//1 HOUSING I V TO TREATEDSITE ISENSOR AT SENSED SITEJ/ PERIODIC SENSING AND DATA EVALUATION ANDDOSAGE CONTROL 265 I IMPLANTED I I I l l I l I I [MEDICATION STORAGE]HOUSING I 66 DOSAGE DOSAGE DISPENSING 67 (SB/DISPENSING TO TREATED SITEFIG 5 U.S. Patent Dec. 2, 1975 Sheet 4 of? 3,923,060

FIG. ID a) a ISO IMPLANTED HOUSING SENSOR AT SENSED SITE SPECIALMEDICATION TIMED MEDICATION E PERIODIC SENSING AND DATA EVALUATIONCIRCUITRY BATTERY-POWER SOURCE FIG. 11

U.S. Patent Dec. 2, 1975 Sheet 5 of 7 ELECTRONIC AND POWER PACKAGESOURCE FIG. 14

FIG. 14A

ELECTRODE SEN SOR AMPLIFIER I R-R INTERVAL ORS ANALYSIS AND DETECTORCOMPARISON TO CONTROL VALUE ORS PERIOD ANALYSIS AND COMPARISON TOgONTROL VALUE MEDICINE NEED AND/OR TOXICITY EVALU ATOR Q PUMP CONTROLFIG. 15

HOURS: 241 2 3 4 5 6 7 8 QIOII I2 13145161718 192021222324 CONDITION ICONDITION ]]I CONDITION JI REGULAR POTENTIAL" ACTUAL EXTRA 2-I-IOUR DOSEI DOSE ON I=DOSE HOURS,

SCI-IEDULE TIME DEMAND TIME EVERY 8 HOURS ELECTRODE SENSOR FIG AMPLIFIERQRS IDETECTOR POSSIBLE QRS- COMPLEX DETECTOR I POSSIBLE QRS-COMPLEX IEND DETECTOR COMPLEX DETECTOR TRUE QRS- J POSSIBLE QRS- COMPLEX STARTDETECTOR QRS PERIOD ANALYSIS AND COMPARISON TO CONTROL] VALUE MEDICINENEED AND/OR l TOXICITY l EVALUATOR PRESENT DAY R-R STAT U S PREVIO US DAR-R STAT U S TWO HOUR MEMORY EIGHT HOUR o R E AE O W W A R w mm HSS TSRO.I N AR IUPT E RAMN WT .NOO AA RACC G n h I "am DE e MN m NM PR I 7A6 REJ4 5 IIII R J I/|l|l|| I II|I H m i G 5 mm R I. GD Y N mm LI M IIAOE ECIimp M WEE 2CW IMU LR 1 m mm 1 W S I.\ g m TI L m R an n 25s PER I-IRCLOCK CLOCK MEMORY TIMING CONTROL APPARATUS AND METHOD FOR IMPLANTEDSELF-POWERED MEDICATION DISPENSING HAVING TIMING AND EVALUATOR MEANSBACKGROUND OF THE INVENTION 1. Field of the Invention This inventionpertains to dispensing medical or physiological substances or matterinternally and more specifically to implanted apparatus for dispensingthese substances over a long period of time according to the specificneeds of the patient at the times the substances are dispensed.

2. Description of the Prior Art A review of prior art practices withregard to dispensing medical substances internally of the body is givenin my prior US. Pat. No. 3,692,027 to which reference is made. So far asI am aware, my prior US. Pat. No. 3,692,027 provides the first teachingof a self-powered device which can be implanted and which is adapted todispense medical substances in pre-measured doses at specific intervalsover a long period of time. There has appeared in the June 1973 issue ofFortune maagazine an article describing other continuous diffusioncapsule types of dispensing devices. This article points out andemphasizes the tremendous need for long term medication dispensingdevices which can provide for dispensing of medication at specifictarget organs or target sites. The prior art in the area of diffusiondevices is also illustrated in US. Pat. No. 3,379,996 by David Long andMoses Folkman for a polysiloxane carrier for controlled release of drugsand other agents. The device of this patent consists of a siliconerubber container with the drug being soluble and capable of diffusingthrough the silicone rubber to the outer surface of the container. Afurther development of this device was reported in the literature in theAnnals of the New York Academy of Sciences, vol. 111, 1963-64 on pages857-868 by Judah Folkman and David Long in which an electrical voltageis described as being ap plied to the container and to an outsideelectrode, in an attempt to increase the diffusion of materials throughthe fibrous scar tissue which is caused to be thrown up around thecontainer by reason of its being implanted into the myocardium. Themedication is described as being pulled through the myocardial fibrousscar tissue by means of iontophoresis. In these adaptations, themedication is in a continuous diffusion state and is not presented indiscrete doses at timed intervals or according to the physiologicalneeds.

Related to the present invention is the practice of implanting deviceswhich sense heart conditions by means of the cardiac electrical activityand trigger electrical pulses to effect the heart rate according to thesensed data. These devices have generally been categorized as pacemakersand their use proves that the human body can accept implanted deviceswithout endangering human life in the implantation procedure. They havealso provided documentation for the applicability of feedback in theinstance of the demand pacemaker version in which the output iscontrolled by the pacemaker logic which makes decisions on the basis ofthe electrical activity of the heart. The feasibility of the demandpacemaker for implantation is documented in the articles listed below.

1. Goetz, R. H.; Goldstein, J. V.; Frater, R. W. M.,

Berkovits, B. Demand Pacemaking in Intermit- 2 tant Heart-Block, Journalof the American Medical Association, Vol. 10, pp. 657-662, 1968.

2. Nathan, D. A.; Center, 5.; Wu, C.; Keller, W.; An Implantable,Synchronous Pacemaker for the Long Term Correction of CompleteHeart-Block. Circulation, Vol. XXVII, pp. 682-685, 1963.

3. Fischler, H.; Barr, I. M.; Auerback, Yerushalmi S.; Neufeld, H. N.Atrial-sychornized Demand I-Ieart Pacing. IEEE Transactions onBiomedical Engineering, Vol. BME-16, pp. 64-69.

A further area of the prior art related to the invention concerns thevarious types of sensors some of which are now commercially availableand which can be used to accurately sense physiological and chemicalbody conditions. At present, the output of most of these devices thatsense body changes are recorded and/or acted on by devices external tothe body. For example, glucose detection, pI-I detection, ionic changedetection, blood pressure or blood flow detection, electrical activitydetection, respiratory detection, and gastrointestinal motilitydetection all constitute existing practical types of sensing apparatus.

It should also be recognized that the prior art has shown that animplanted device having a battery supply can be electrically rechargedwithout having to remove the device. Also, my own US. Pat. No. 3,692,027refers to means for recharging an implanted medication supply. Thus,both implanted battery and medication storage recharging are known.

From the foregoing, it can be seen that while the implanting techniquehas been perfected in many respects, and that while both the diffusiondevice which releases medication continuously and my own selfpoweredtechnique which provides a means for dispensing medical substances inpre-measured doses on a continuous basis or at predetermined regularintervals, no dispensing device or method has appeared in the prior artwhich allows medical substances to be dispensed by an implanted deviceand according to specific physical requirements of the patient that aredetermined by the device itself.

SUMMARY OF THE INVENTION The apparatus and method of the invention isbased on the apparatus being entirely implanted in the body. There isprovided either one or a plurality of sensors, each of which is adaptedto sense a particular body condition at a particular point in the body.There is also provided a self-powered medication dispensing apparatuswhose operation is made dependent on evaluation of changes in the senseddata. The dispensing apparatus and method of the invention can bedirected to one or a plurality of medical substances inpowdered, liquid,suspension, or other dispensable form. The decision making capability ofthe invention which functions on a basis of changes in the sensed data,controls when the dispensing apparatus operates and therefore controlsthe dispensing of medication according to the specific needs of thepatient at specific times.

DESCRIPTION OF THE DRAWINGS FIG. 1 is a block diagram illustrating thebasic components of an apparatus according to the invention.

FIG. 2 is a block diagram illustrating the application of the inventionto cardiac monitoring and medication.

FIG. 3 is a block diagram illustrating the application of the inventionto blood pressure monitoring and medication.

FIG. 4 is a block diagram illustrating application of the invention toblood chemistry monitoring and medication.

FIG. 5 is a block diagram illustrating application of the invention todispensing medication to the same site from multiple sources.

FIG. 6 is a block diagram illustrating application of the invention todispensing different medications to different sites.

FIG. 7 is a somewhat schematic and enlarged diagram of a minaturebellows pumping device useful in the invention.

FIG. 8 is a somewhat schematic enlarged view of a multiple bellows typepump for dispensing the same medication to the same site but indifferent quantities and under different conditions.

FIG. 9 is a somewhat schematic enlarged diagram of a multiple bellowstype pump for dispensing separate kinds of medication to separate sitesin different quantities and under separate controls.

FIG. 10 is a somewhat schematic enlarged drawing of a bellows pump withmultiple separated chambers for different chambers or sites having acommon power source.

FIG. 11 is a somewhat schematic enlarged view of an implantable systemaccording to the invention and adapted to dispense different medicationsfrom different sources under different controls.

FIG. 12 is a schematic diagram of the apparatus of the invention as itmight be used with superventricular tachycardias treated with quinidine.

FIG. 13 is a schematic sectional view through the apparatus of FIG. 12.

FIGS. 14 and 14A schematically illustrate a portal arrangement forreplenishing medication to the system.

FIG. 15 is a block diagram of the decision making circuitry.

FIG. 16 is a more detailed circuit diagram corresponding to FIG. 15.

FIG. 17 is a representative timing diagram for dispensing plural dosesof medication.

BACKGROUND FOR LATER DESCRIPTION OF THE PREFERRED EMBODIMENTS Prior todescribing the apparatus and method which constitutes the invention,background information will be given concerning specific and recognizedmedical problems to which the invention method and apparatus may beapplied. With this background, the mechanisms and methods laterdescribed will be better understood.

The general concepts behind the applications to be explained revolvearound sensing and evaluation of biological signals that relate toabnormal processes or variations in normal processes in the body thatmay be used to evaluate the need for release of the given medication,hormone, or other type of chemical into the body or into specific organor target sites. The dispensation of medication into specific organsites, by the means of a small catheter, may of course allow for smallquantities to be much more potent at the target site without systemicside effects developing. In addition, the concept of feedback evaluationcontrolling or altered release of medication will allow for anintermittent dispensing of the drug which might handle a problem at muchlower doses than if medication is given over a sustained period withoutsensitive regard for therapeutic needs and the possible development ofvarious toxic and tolerant effects. For example, an application thatwill be described later is that of transducing a pressure change in theblood vessels to provide information to the decision making capacity oflogic and timing circuits in the device which activate a self-poweredpump, to release a given quantity of a blood pressure reducingmedication. The decision to dispense the medication is intended tooperate only when the pressure rises above a certain level. This type ofoperation offers the opportunity to help overcome some of theundesirable effects from drugs such as adrenergic blocking agents, whichwhen given chronically produce untoward side effects, includingpsychological depression and orthostatic hypotension. The same is truewith a variety of other blood pressure reducing drugs. In otherapplications to be described later, physiological signals that predictthe toxic effect of a given drug can be used by the device in evaluatingthe needed medication dispensation. Thus, the toxic effects can becounterpointed against the therapeutic need for medication by the logicsystem of the invention.

Involved in the biological sensing for blood pressure or otherphysiological changes that the device is evaluating, are possibletraining of physiological responses, effects or behavioral modificationeffects, by means of appropriate programming of such a device with smalllogic circuits. The type of signal detected and used for processing inthe logic circuits may be either one signal or a combination ofbio-signals, one orseveral being necessary for the triggering of thelater described pump dispensing device. For example, by implanting anappropriate device in drug addicts one may monitor a variety ofphysiological changes produced by the injection of a narcotic; that is,respiratory depression measured by a micro strain gauge attached to thediaphram, a strain gauge attached to the stomach or in the upperduodenum to measure gastro-intestinal motility and the type of motility,and a pressure transducer to measure the increase in biliary ductpressure, and use the combination of these signals to detect theinjection of a narcotic; the dispensing pump may then release a narcoticantagonist and/or, for behavioral training, may release a drug thatwould cause nausea and vomiting, thus providing for behavioralmodification or avoidance conditioning.

The types of application uses with evaluation of biological signalsaccording to the invention include: 1) chemical transducers and feedbacksuch as glucose detection, pH detection, ionic change detection; 2)temperature, pressure, or mechanical transduced changes; for example,blood pressure, blood flow gut motility; and 3) electrical activity asmight be measured in the electrocardiogram or electroencephalogram. Inthe electroencephalogram and electrocardiogram, special logic circuitsmay be devised according to the invention on a minature basis to providefor analysis of abnormal signals or rhythms and then the dispensation ofa given amount of drug into the specific target organ. For example, withcertain cardiac arythmias, the invention recognizes that it is possibleto detect and evaluate these abnormalities with fairly simple logiccircuits and then to dispense a drug into the pericardial sac in asimti-hypertension drugs have been more effective than this. What thisinvention provides is a method for treating malignant hypertension thatis based on sensors inside the body and medication pumped to variouseffector sites. The sensors may include 1) blood pressure detectingdevices in the neck and/or in the lower extremities; 2) electricalactivity from the carotid sinus or aortic body; 3) possible electricalactivity from the sympathetic outflow; and 4) the electrocardiogram.Blood measurements allow the mechanism of the invention todifferentiate, for example, between the dystolic and systolic ratios.Combinations of information from the sensors may be programmed inmicro-miniature logic circuits to provide a series of treatmentdecisions based on the individual characteristics of the patient.

On the effector side, the physician is given a wide choice with thepresent invention of attacking the problem of malignant hypertension inseveral sites: 1) the sympathetic outflow can be blocked with ganglionicblockers; 2) the adrenal outflow or releasing mechanisms can be blockedwith ganglionic blockers; 3) appropriate drugs are available which canbe dispensed systematically to block the adrenergic receptors throughoutthe body; and 4) another group of drugs known as the varatrum viridecompounds are available and which may be dispensed according to theinvention to inhibit the pressure centers in the brain itself. Takingonly two of the mentioned examples, it is now possible to deviseeffector sites in l) the sympathetic chain or outflow and 2) systematicsites via intraperitoneal dispensation. Using four sensors and twoeffector sites it is now possible to set up an array contingencies, onlysome of which will be described. For example, if the dystolic bloodpressure increased beyond a certain point, the systemic circulation,actually a site in the interperitoneal cavity, may receive a dose ofbeta adrenergic blocker antihypertensive medication; in addition, bymeans of carefully monitored release of drugs to the sympathetic outflowvia a catheter, it is now possible to increase the effectiveness of theantihypertensive drugs by blocking this outflow. As discussedpreviously, this local application could help to prevent many of theserious side effects of systemic ganglionic blocking medication.Problems in hypotension may be monitored with neck blood pressuredevices or with the electrical activity from the carotid sinus. Variousfeatures in the contingencies may be based on the normal exercisepatterns of the individual, for example, in persons who have a heavyexercise load, the logic mechanism of the invention may be establishedto respond only after 2 to 3 or even 4 hours of increased dystolicpressure thus allowing for extended periods of exercise with slightlyincreased pressures. Combinations of the devices shown in the drawingsmay be used to supply drugs at the various effector sites.

In one specific adaptation a blood pressure sensor picks up both thesystolic and dystolic blood pressure levels which are then amplified, orat least the analog signal is amplified, and presented to a detector andlogic timer system using micro-miniature logic systems in which severaldecisions are made:

1. Is blood pressure above criteria level less than 30% of theheartbeats over a given period of time? If the answer to this isnegative, then there is no release from the later described pump system.The reader should keep in mind that the pump system might operate 6times a day, or alternately, it could operate twelve times a day, thusmedication decisions 6 could be made every 2'o r 4 hours or even infractions of hours.

2. IS the blood pressure above criteria level more than 30% of the time?If so, the medication is re- 3 leased into the systemic system.

3. Is the blood pressure above criteria more than of the time? We wouldexpect that the decision would be affirmative only arare number ofoccasions, but if the decision is affirmative then there is a release ofanother durg, a ganglionic blocking agent directly to the sympatheticoutflow in the sacral region and the first five of thethoracic lumbarThe self-powered dispensing device of the invention allows for two majorchanges in the treatment of hypertension: I) It allows for dispensing ofthe drug to a selective site inside the body, thus reducing many of theside effects of more potent and hypertensive drugs. 2) It allows for amuch more careful titration of the hypertensive effects of the drugs,thus cutting down on the number of unwarranted hypotensive episodes,especially those associated with postural hypotension. One means bywhich this may be accomplished is by selecting the drug used for itshypotensive effects for shorter duration of action, thus allowing forblood pressure feedback to regulate dosage.

One notable example of the foregoing is in the treatment of severehypertension. Currently the drug most often used in the treatment ofsevere hypertension is guanethidine, which is a long-acting drug thattends to accumulate in tissues and is excreted slowly. Leaving off adose of this medication would not have a major effect for several hours,thus the.- potent side effects could continue for a considerable periodof time. Such drugs as bretylium, a short-acting hypertensive agent,have now been abandoned because of their potent side effects and poorabsorption after oral administration. These effects may, however, betitrated in the self-powered dispensing device of the invention. Inaddition, other drugs similar to this compound, for example Bethanidine,(l-bensyl-2, 3-dimethylguanethidine) and other congeners may be used toa much better advantage by means of selective titration which lendsitself to the apparatus and method of the invention.

The other group of drugs that increase efficacy depend on the selectiveability of the device of the invention to dispense medication in aparticular site and which group includes the ganglionic blocking agentssuch as hexamethonium and related compounds. Blockade of the sympatheticganglia has a marked interrupting effect on the adrenergic control ofarteriols and results in vasodilation and improved peripheral blood flowof vascular beds and a fall in blood pressure. Part of the potency ofthese drugs is related to the low ratio of preganglionic axons topost-ganglionic axons. Thus, ganglionic block has a very potent effect.The major difficulty with the ganglionic blocking agents is anon-selective effect on both parasympathetic as well as sympatheticganglions. Again, this group of drugs is poorly absorbed from thegastrointestinal tract, and there is a limited ability of thesequaternary ammonium ions to penetrate cell membranes in general. Bydirecting the outflow portal of a polyethylene catheter from thedispensing device of the invention to the sacral ganglion and to thefirst four ganglia of the thoracolumbar outflow the physician mayselectively block blood vessels in large muscle of the extremitieswithout major effects on the gastrointestinal tract, genitourinarysystem,

or the heart and lungs.

Cancer is another problem that may be helped with the inventionsmethod-and mechanism. For example, there may be a need to dispensedifferent types of drugs to different body sites depending on the sitevulnerability. The bior tri-partite bellow bags, later described, may beused for this purpose. In other applications, the radio-activity ofcertain radio-active anticancer compounds may be monitored and the drugdispensed dependent on the radio-active concentrations in a given cancersite.

Another use may be in peptic ulcer or gastric ulcer. For example, the pHmay be monitored in the stomach according to the invention and theantrium of the stomach may be bathed in an anti-cholinergic drug.Another use may be to bathe painful spinal dorsal nerves with medicationin nerve injury triggered externally by the patient but with theavailability still controlled by the inventions timing and logiccircuits to prevent overdose. In this case. the patients capacity toperceive pain would become the sensor. He would activate a reed switchto signal the device. With kidney stones, an outflow catheter may beplaced into the kidney pelvis itself, monitored and used to change thepH of this area to dissolve the stones. Certain forms of epilepsy orperhaps several forms of mental illness may be more effectively treatedwith intraventricular medication or minute doses to a specific brainsite. This medication in the case of epilepsy may be triggered byabnormal electrical activity. Other abnormal brain conditions may betreated by triggering off abnormal slow waves (in the awake state) or byprograms to maintain certain forms of electrical activity such as alphawaves or certain subcortical rhythms. It, of course, should beunderstood that any of the central nervous system applications couldonly proceed after years of careful experimentation.

In the case of certain spastic vascular disease such as Bergers orRaynands disease, it now appears feasible with the present invention toaccomplish a periodic lumbar or cervical sympathetic block withmedication applied to this area. Medication may be applied to the arteryitself by implanting the outflow at the time of vascular surgery.Medication would be dispensed dependent on blood flow sensing.

Congestive cardiac failure may be detected with sensors that pick upvenous pressure and cardiac electrical activity, and controlled withdigoxin fed by catheter directly to the pericardial sac. In otherconditions, depending on the results of extensive research, vasodilatorsmay be dispensed to the pericardial sac by external patient control onthe basis of angina or other perceived or sensed difficulties by thepatient.

Finally, there are a variety of cardiac conditions, especially cardiacarthythmias, that may be treated by dispensing medication into orthrough the pericardial sac in response to abnormal electrical signalsfrom the heart. For example, the device of the invention may dispensequinadine in the supraventricular tachycardia condition based on theelectrophysiological activity of the heart. This example is laterdisclosed to demonstrate the present application of the conceptsdescribed above in a specific device whose operation can be fullydocumented.

In summary, many potential applications present themselves immediatelyand while many years of work will be required by many persons to fullydevelop the invention in all its ramifications, the basic concept is.

also immediately recognized as practical and useful. Those skilled inthe art will recognize that the individual components required and theindividual method steps required have been separately proven in othermedical environments. It is the present invention, however, thatcombines such components and steps together to accomplish results andfunctions not heretofore achieved.

DESCRIPTION OF THE PREFERRED EMBODIMENTS The invention will first beexplained in a broad context and in relation to certain applicationsfollowing which reference will be made to construction details ofspecific components for practicing the invention, then finally onedetailed application will be presented.

FIG. 1 illustrates in block and schematic diagram form the basiccomponents of an implantable system according to the invention. Inparticular, there is provided a micro-power source 28, a medicationstorage 29, a sensor 30, a dispenser control 31, and a dispenser 32. Allof the components except sensor 30 are contained in an appropriatehousing 33 which is implanted in the body of the persons being treated.Power for the system is provided by a suitable micro-power source 28such as described in US. Pat. No. 3,692,027. The purpose of the sensor30 in each instance is to sense some type physiological, chemical,electrical, or other condition in the body at a particular site, andproduce data which corresponds to the sensed condition at the sensedsite. This data, according to the invention method, is then sampled andevaluated by an appropriate dispenser control 31, e.g., a logic circuit,and depending on whether the sensed data is or is not indicative of aneed for medication, the dispenser control 31 will operate in a mannerto cause the dispenser 32 to either remain off or to be operated todispense some predetermined amount of medication from the storage 29according to the patients needs.

Referring next to FIG. 2, there is schematically illustrated a morespecific and somewhat more complex application of the invention tocardiac monitoring and medication. The micro-power source, while notshown for simplification, should be treated as part of the FIG. 2-6systems. In the application of FIG. 2, there is provided medicationstorage 40 and an electric potential sensor 41, such as employed inelectroencephalogram and electrocardiogram examinations. While indicatedas a single sensor, sensor 41 could comprise plural, e.g., three ormore, sensors, The sensed information is directed to an appropriatelogic circuit 42 which is designed to screen the sensed data for keyfactors. Since logic circuits as such are known and within the skill ofthe art to design, the description in general will speak more to themedical aspects than to the precise details of the circuitry, although amore complete circuit disclosure will be provided in one example to bepresented later.

With further reference to FIG. 2, it is known that sensed electricpotential data such as obtained in electroencephalogram andelectrocardiogram examinaput accordingly. Subsidiary circuits 44 and 45can be designed for similar functions with respect to factors B and Csuch that if factors, A, B and C are all outside normal limits an outputis produced at junction 46 and which can be used to control thedispenser 47. Other combinations are possible. All of the componentsexcept the sensor shown in FIG. 2 should be noted as being enclosed in asuitable implantable housing 48.

To illustrate a further application, reference is made to FIG. 3 whichis directed to a blood pressure monitoring and medication system. Inthis application, there is provided a pressure transducer 51 which isconnected to an appropriate logic circuit 52 contained in an implantablehousing 50 and which is designed to make decisions on the basis ofsystolic and diastolic characteristics. If the blood pressure is notwithin the defined limits a no output is produced and which is used tooperate a suitable dispenser 53 having medication selected from storage54 to reduce the pressure.

.In FIG. 4 a chemical monitoring system is illustrated. In thisembodiment a suitable chemical level sensor 60 is employed and which,for example, may sense pH changes, ionic changes, glucose level or otherbody chemistry factors susceptible to sensing. The sensor 60 isconnected to an appropriate threshold discriminator and logic circuit 61which in turn is connected to a medication dispenser 62 and all of whichcomponents except the sensor are contained in a suitable implantablehousing indicated by 63 which also houses the storage 59. In thisapplication, the logic circuit 61 determines whether the sensed chemicalfactor is or is not within an acceptable threshold and, if not, operatesthe medication dispenser 62 to bring such factor within an acceptablethreshold.

Making reference next to FIG. 5, there is shown in block diagram form anapplication of the invention wherein dosages of the same medication maybe dispensed from different sources. In this embodiment, the sensor 64is connected to appropriate logic circuitry 65 which controls periodicsensing, evaluation of the sensed data and dispensing of medication froma common medication storage 66 through a dispensing means 67 or aseparate dispensing means 68. For example, dispensing means 67 mayconstitute a low volume, regularly dispensed medication whereasdispensing means 68 may be used for supplementary medication at the sametreated site.

In FIG. 6, the sensor 70 is connected to the appropriate logic circuit71 which controls a dispensing mechanism 72 for dispensing from a drugstorage 73 having, for example, a drug A. Circuit 71 also controls thedispensing mechanism 73 for dispensing from an alternate drug source 74,for example, drug B. In this application it can be seen that differentmedications can be dispensed to the same or different treated sites withone medication being for one purpose and another medication being foranother purpose. Housing 76 encloses the apparatus.

From the foregoing description, it can be seen that the variousapplications of the invention will each require appropriate timing andsensing devices, appropriate circuitry for evaluating and makingdecisions about the sensed data, and appropriate dispensing devices fordispensing medication subject to the evaluation of the sensed data.Implantable sensors for a great variety of purposes are well known andthose skilled in the art will quickly appreciate their applicability tothe broad concept embodied in the present invention. Those skilled inthe art will also readily ascertain other types of implantable sensorswhich are suited and the required parameters for other types of sensors.

Considering next the type of logic circuitry required, given the conceptof the invention, the design of such will be readily apparent to thoseskilled in the art. In general, the logic circuitry will be of a type ineach application suited to receiving sensed data from a sensor, e.g., atransducer, in a form corresponding to the particular application, e.g.,pressure data, chemical data, electrical data, et cetera, and producingan output depending on the data evaluation. In some instances, aspreviously noted in connection with FIG. 2 there may be a plurality ofoutput data on a single output which can be screened by differentsubsidiary circuits for different data, e.g., factors A, B and C, as inFIG. 2. Miniature logic circuits of the kind required by the presentinvention may be found in both in design books as well as inn medicalliterature, e.g., designs for demand pacemakers. Those skilled in theart will also readily appreciate the fact that the present invention isof such wide scope that the logic circuit designer is given a widechoice in the types of circuitry which may be used to perform the logicfunctions.

Another important consideration concerns the implantability of thesensor employed, the implantability of the housing which houses themedication storage and dispensing apparatus and the implantability ofany catheter or other device employed to discharge the medication at thetreated site. Since sensors, particularly electrical sensors, long termimplanted diffusion devices, and the like, have all been used and theimplanting problems are well known, the parameters required forimplanting are considered known to those skilled in the art. Also, sincepacemakers have been implanted, the general parameters for implanting ahousing of the type required by the present invention is also wellknown. The long term discharge of medication internally throughimplanted catheters, and the like, fed by external sources of medicationis also a current practice. Thus, tissue growth problems, tissueblockage problems, and the like, of the kind encountered in priorpractices are contemplated by the present invention and the sametechnology previously developed will be useful in the present invention.

Each application of the invention requires means for storing a treatingsubstance under pressure in powdered, liquid, or other dispensable form,means for pumping or otherwise removing predetennined portions from suchstorage and means for directing the measured dosage to the appropriateorgan or site best suited to receiving the dosage. The amount ofpressure may vary with the medication because of different viscosity,dose sizes, etc., and many arrangements known in the pumping art willsuggest themselves. For example, the medication may be enclosed in anelastic sack by introducing an inert gas within the storage area toassert pressure.

The most immediately available device suited to the invention forstoring and dispensing medication is illustrated in my prior U.S. Pat.No. 3,692,027. For example, such a device as shown in my prior patentmay constitute the dispenser 32 illustrated in FIG. 1 and the dispensercontrol 31 in FIG. 1 may include a switch device connected so as toconnect and disconnect the battery .which is used to power the device ofmy prior patent. In

this application, the sensor 30 of FIG. 1 senses the particularcondition at timed intervals and the dispenser control 31 of FIG. 1causes the dispenser mechanism, such as illustrated in my prior patent,to either operate or not operate according to the evaluation anddecision based on the sensed data. Appropriate controls are preferablyprovided for in the circuit logic to prevent overdose if the sensedphysiological change does not occur quickly enough in response to themedication dosage, e.g., appropriate timing delays or dose/timefunctions.

The invention readily lends itself to a variety of dispensingmechanisms. Mention has already been made of the mechanism described inmy prior U.S. Pat. No. 3,692,027. Another mechanism for pumping fluidmedication is shown in FIG. 7. In FIG. 7 there is shown in a highlyenlarged form a housing 80 mounting a piston 81 secured to a bellowscontainer 82 made of polyvinyl or other suitable material. A rod 83attaches to piston 81 and is caused to move inwardly by an appropriatesolenoid 84 and to move outwardly by an appropriate spring 85 actingagainst a head portion 86 as schematically represented in FIG. 7.Solenoid 84 is, of course, controlled by an appropriate logic control aspreviously explained. The bellows 82 receives medication through aninlet tube 87 and a one-way valve 88 and discharges such medicationthrough a one-way valve 89 and a discharge tube 90. It should, ofcourse, be understood that the pump structure shown in FIG. 7 will inpractice be contained in the implanted housing previously referred toand has the particular advantage of not requiring a high frictionproducing seal between piston 81 and housing 80 since all medicationwill be sealed and confined to the interior of bellows 82. Bellows pumpsas such are known and proven.

One problem common to many types of physical disabilities is the need todispense a daily average dose, e.g., insulin, on a regular basis and todispense intermittently dosages for short acting drugs, e.g., insulin,when need arises. FIG. 8 schematically represents a device suited tothis requirement. In particular, cam 100 is driven by a suitable micropower motor such as shown in my prior U.S. Pat. No. 3,692,027 and whichis arranged to be energized through an appropriate logic circuit, notshown. Rotation of cam 100 engages roller 101 and forces arm 102 to movepiston 103 which causes the bellows 104 to discharge from the drugstorage area 105 a predetermined dosage previously obtained from a drugstorage 106. As cam 100 rotates and after discharge bellows 104 retractsand refills the chamber 105 at a suitable time the control for cam 100causes it to stop. Appropriate one-way valves 107 and 108 control theintake and discharge. Such a cam driven arrangement may thus provide therequired daily average dosages. For intermittent additional needs, asolenoid 110 is connected to the appropriate logic circuit, not shown,and when energized will move arm 111 and operate piston 112 to provide alesser amount than is obtained by cam 100 so as to provide a smallerdosage. Solenoid 1 is de-energize'd at the end of the discharge strokeand spring 113 causes the storage area 114 to refill.

In FIG. 9 there is indicated an arrangement for discharging twodifferent types of medication. In FIG. 9, cam 120 and solenoid 121should be considered similar in their operation to the cam and solenoidoperations previously explained in connection with FIG. 8. In the FIG. 9application, the cam 120 operates on the bellows 123 and solenoid 121operates on the bellows 124. In the FIG. 9, as well as in the FIGS. 7and 8 dispensing arrangements, power for the respective drive members,e.g., rod 83, cam 100, is provided by the previously mentionedmicro-power source. One type of medication, e.g., a long acting drug,may be stored in one storage reservoir 125 and a separate medication,e.g., a short acting drug, may be stored in a separate storage reservoir126. Thus, one drug source may be dispensed by use of solenoid 121 andanother drug source may be dispensed by the use of cam 120. It will, ofcourse, be understood that appropriate one-way valves and other featuresof known mechanical construction may be employed even through not shownor specifically explained.

In FIG. 10 there is shown a reservoir arrangement comprising a bellowswith two compartments 130, 131 housed in a common housing 132 andoperated by a plunger piston 133. From the drawings, it can be seen thatthis arrangement, like that shown in FIG. 9, provides for dispensing twoor more types of medication to two or more body sites. The FIG. 9arrangement allows such medication to be dispensed to two sites atdifferent pressures using two power sources whereas the FIG. 10arrangement provides for the medication to be dispensed to two or moresites at unequal pressures using only one power source. In addition, themultiple chamber bellows of FIG. 10 provides for a two or more drugdispensing capability without the greatly increased friction of morecylinders and pistons. The bellows chamber in addition to its sealingfunctions allows for a vairety of options at the time of implantingsurgery simply by substituting various bellow configurations in thepump. This means that the surgical facility does not have to maintainmany types of more expensive total pump configural changes. It isanticipated that a large variety of bellow shapes and sizes will befound useful and which can be substituted in the pump cylinder for amultitude of treatment purposes.

In FIG. 11 there is schematically shown a system of a type whichcorresponds with the type of application diagram in FIG. 6. Here againit should be understood that the schematic diagram in FIG. 11 would, inpractice, correspond to a device of substantially less physical size. Inparticular, there is represented in FIG. 11 a housing having appropriatesuture anchors 151. Within the housing 150 there is provided anappropriate compartment 152 for holding some predetermined amount ofmedication intended to be released over a long term for a chronicsituation requiring regular dosages whose size can be predetermined andscheduled. The compartment 153 represents a storage area for specialmedication such as might be required by unusual and transient conditionsin a specific patient. The previously mentioned evaluating and controlcircuitry is indicated as being confined in a separate compartment 154and which is connected to an appropriate sensor 155 located within thebody being treated but external of the housing 150. For the timedmedication a micro-powered unit of the type shown in my prior U.S. Pat.No. 3,692,027 is controlled by the circuitry in compartment 154 and whenindicated by evaluation of information coming from sensor 155, unit 160turns on and rotates the cam 161 thus driving the' cam peaks againstroller 180 attached to the shaft of piston 162 so as to discharge themedication confined in the storage area 152 through an appropriatedischarge tube 164. During discharge the flap valve closes as piston 162moves to the right in FIG. 11 and a sliding cylindrical valve member 171moves upwardly 13 in FIG. 11 so as to allow communication between pipes175 and 176. As cam 161 continues to turn roller I80 contines to ride on.cam 161 by reason of spring 181. Flap 170 opens, sliding valve 171moves down and a new charge is stored in the storage area 163. portals158, 159 provide for refilling.

When there is a demand for special medication as determined by sensorevaluation with the logic circuitry in compartment 154, solenoid 190 isenergized which causes piston 191 to move to the left in FIG. 11 againstthe tension of spring 192. Flap valve 193 closes, sliding valve 194rises as shown in FIG. 11 and pipes 196 and 197 are placed incommunication to allow discharge through pipe 164. On the return strokesliding valve 194 moves down, flap valve 193 opens and a fresh charge ofthe special medication is drawn into the storage area 200. Thus, byenergizing and de-energizing the power unit 160 the treated body can beprovided with the periodic timed medication and by energizing andde-energizing the solenoid 190, the treated body can be provided withthe special medication.

There is next given a more detailed disclosure directed to a cardiacpump mechanism to dispense medication for prevention of recurrenttachycardias. As background, it should be noted that quinidine is givenon a chronic basis for the prevention of recurrences of artrialfibrilation and flutter as well as supraventricular tachycaridas not dueto digitalis toxicity. Quinidine is also effectively used, as well asprocainamide, in prevention of recurrences of ventricular tachycardia.Quinidine is also used to prevent recurrences of ventricular fibrilationexcept when ventricular fibrilation occurs during complete heart blockin which case it is contraindicated. A discussion of treatment ofcardiac arrythmias can be found in Drugs used in the Treatment ofCardiac Arrythmias in Treatment of Heart Disease in the Adult, 2ndEdition, Rubin, T. L.; Gross, H.; Arbeit, S. R., Lea and Febriger,Philadelphia, pp. 297-324, I972. One of the difficulties in using thesedrugs is that the therapeutic index, the ratio of therapeutic dose totoxic dose, is quite low. The pump feed back system of the invention is,however, adapted to carefully monitor the state of the heart and toxicmanifestations of the drug and maintain the drug dosage at a leveldesigned to minimize, if not eliminate, complications attributable tothe medication. Thus, the device and method of the invention allows moregeneral use of these medications in what are quite severe andlifethreatening conditions of the heart. The invention is directed towhat is needed, namely, a feedback evaluation system that will providefor the maximum needed therapeutic dose that can be maintained below thetoxic manifestations of the drugs.

The described goals can be accomplished by monitoring the diseasecondition and regulating the medication to treat the condition accordingto the invention and yet steering clear of the toxic manifestations ofthe drug by monitoring and regulating the dose in relationship to thesemanifestations also. The disease entity to be treated as an example isthe supraventricular tachy cardias. The present example is directed tocounterpointing the heart rate against the toxic changes produced byquinidine, that is widening of the QRS Complex (a component of theelectrocardiogram). The dose of quinidine can thus be monitored by useof the invention and reduced when there is prolongation of the QRScomplex which occurs as the dose of quinidine begins to reach thethreshold for toxic effects.

FIGS. 12 and 13 demonstrate the basic construction and operation of thedevice to be used with supraventricular tachycardias treated withdispended quinidine. The pump motor 210 is of the type shown in my US.Pat. No. 3,692,027 and is set to turn the equilateral cam 211, e.'g.,eight or more revolutions per day, thus providing a total of 24potential cam pump activating contacts with the roller 230 whichoperates piston 212. Thus, the pump can potentially operate every hourof the day providing for 24 potential doses per day. Using this paradigmprovides the following options, if one operates on a 2-hour dispensingschedule, that is dispensing medication every two hours unless alteredby decisions based on evaluation of the sensors (the 2hour schedule isaccomplished by turning off the pump motor 210 every other hour): 1. Themechanism would dispense very two hours as an average dose timing. 2.Depending on the feedback evaluation, it may suppress a dose ofmedication for 2 hours thus leaving a 4 hour interval between doses whenthis is indicated. 3. Extra doses can be dispensed on a one hourschedule if needed. In actual operation the movement of pump motor 210will turn the cam 211 and dispense the first dose. Then the timingmechanism cuts off the mechanism for one hour unless conditions requirethat an extra dose of medicaion be provided and in this case themechanism is designed to continue to operate for the next hour toprovide an extra dose. Thus, under normal operating conditions, themechanism will provide 12 daily doses every two hours. Should toxicconditions of quinidine manifest themselves, then the mechanism may becut off for sufficient time to increase the interval between medicationsto four hours.

In actual practice with a supraventricular tachycardia, the electrodes250 shown in FIG. 13 on the heart itself pick up electrical activity ofthe heart and conduct the heart signals to amplifiers in the electronicpackage by wires 251 embedded in the catheter 248. An electronic logicrecognition program provides for identificationof the QRS complex andanother program subsequently quantifies the ORS period and R-R intervalas described in relation to the chart shown in FIG. 17. Operationally,the cardiac frequency (R-R interval) is monitored and averaged for eachhour over the 24 hour period and stored in a register. The lowestfrequency average for an hour during the 24 hour period is compared withthe lowest frequency hour from control periods as to whether this hasincreased by 10 to 20 percent over criteria control levels whichcriteria are set at time of implantation. Thus, if the frequency hasincreased by 20 percent, then the mechanism will provide three extra 1hour doses every 8 hours for the next 24 hours. The decision-makingcontrol logic in the system provides for this operation. The contrastingconcern, that of quinidine toxicity, is monitored by the QRS period. TheQRS period is sampled and evaluated each hour and if it increases overcriteria levels of control) or if premature ventricular contractionsdevelop (indicated by very wide QRS complex over l50% of control)especially with the quinidine effect controlled, then the next doseperiod is suppressed by cutting off the power to the pump motor 210 andsecondly stops the extra dose for that 8 hour period that is currentlyoperational because of the criteria provided for in the first series offeedback options. The chart depicted in FIG. 17 is explained as follows:Condition I Normal operation-pump operates every two hours on evenhours.

15 Condition II Cardiac frequency has increased by 10-20% which actuallymeans the R-R interval has decreased by l-20%. In practice, the hourwith the lowest frequency for the previous 24 hour day is compared withthe control value to make this decision. Then, if this 24 hour lowesthour frequency is l020% higher than control, the logic provides forthree extra doses the next day given every 8 hours at l, 9, and 17hours. Condition III The sampled QRS period over the past hour isgreater than criterion levels on the following basis; the QRS complexperiod is sorted on the basis of percent of contol value and given aweight in the following schedule:

I. l or less than control value given weight of 0 2. l l0l20% greaterthan control value given weight of l 3. I-l greater than control valuegiven weight 4. 130-150% greater than control value given weight 5.Greater than 150% of control value indicates ventricular prematurecontraction and is given a variable weight of 8 or l6. If over the hour,out of the 256 sampled QRS periods the weights add up to 256 or greater,then the pump is turned off for the next even hour operation andsecondly stops the extra dose for that 8-hour period that might becurrently operational because of criterion provided for in condition II.Thus, if the hour 4 dose was deleted, then the dose provided for at hour9 would be deleted also.

Other aspects of FIGS. 12 and 13 that require explanation are the threeinput portals 252, 253, 254. Input portal 252 represents an eightposition rotary switch and a needle contact. The rotary switch andneedle contact operates by use of a solid core needle, not shown, with around to triangular to round O.D. (outside diameter) tip section whichis inserted into portal 252 which has a mating triangular hole as shown.Operation of the switch is accomplished by turning the needle throughone to eight of the various positions. Contact to the switch functionare through contacts on the three triangular surfaces of the needleapproximated to the triangular hole contacts. The leads to the needletriangular surface are conducted down the long axis of the needle andare shielded by a suitable isoelectric material. Position No. I of therotary switch provides for battery recharge through the needle contacts.Position No. 2 provides for monitoring the electrocardiogram from theimplanted electrodes. Position No. 3 provides for stimulation throughthe cardiac electrodes if pacemaking functions are needed. Position No.4 provides for contact with the logic system for calibration of thelogic of the cardiac response parameters. Position No. 5 provides formonitoring the logic output and number of doses per day. Position No. 6provides for cutting off of the entire system. Positions Nos. 7 and 8are for future options.

Catheter access portal 253 is a bypass catheter inlet and provides thefollowing functions: (I It allows the physician to exert increasedpressure if mechanical block occurs in the catheter. (2) It allows thephysician to introduce a wire stylet if mechanical block occurs in thecatheter. (3) It allows the physician to introduce additional drugs intothe pericardial sac if needed. The catheter access portal operates in amanner best explained by reference to FIGS. 14 and 14A. A hollow boreneedle, not show, with a round to square to round 16 OD. tip section isinserted through the patients skin with the aid of protuberance 306 andthence into the square hole 303. The square needle segment engages thesides of the square hole 303. Rotating the needle about its long axisrotates pinion 302, which is meshed with and rotates partial ring gear301. When partial ring gear 301 has rotated to its counterclockwiselimit portal 307 is in line with the ID. (inside diameter) of the needleallowing access to the catheter 304, and the pump output port 305.O-rings 308 and 309 seal the port in both open and closed configuration.Pinion 302 is held in position by top plate 310. In FIG. 14, the external casing of the device is represented by line 311.

For purposes of replenishing medication, the input portal 254 isemployed. Since the introduction of pressurized replenishing medicationhas been previously discussed in my US. Pat. No. 3,692,027 and asuitable portal structure described, no further detailed description ofthis operation or of the refill portal is deemed necessary.

FIG. 13 shows in further detail the bypass system with the details ofthe attachment of the catheter system to the pericardial sac. O-rings255 beneath the entry portal are provided for sealing purposes. A onewayvalve 256 in the catheter leading to the pump provides for block of anyincreased pressure in the bypass system into the pump mechanism. Thecatheter system is sewn into the pericardial lining with a ring 247embedded in the catheter 248 having both a uniform catheter section andan appended expanded catheter section in the form of a trumpet 249. Theexpanded catheter diameter provides for increased surface area andreduces any blockage due to the fibrosis around the exit portal to thecatheter. Also shown adjacent catheter 248 are leads 251 leading fromthe pair of sensing electrodes 250 to the amplifier and logic system.These are actually embedded in the catheter and provide additionalsupport for the catheter. The electrodes 250 and attached wires areembedded in a polyvinyl shield after their exit from the catheter.

A block diagram describing the general operation and decision makinginvolved in control of the cardiac medication pump is illustrated inFIG. 15. The depicted electrode sensor and amplifier are intended torepresent standard devices such as are used in present cardiac pacemakercircuits. The remaining portion of the block diagram of FIG. 15 is thebrain of the system and provides control to the pump based on thepresence of conditions I, II or III, as previously described. The typeand nature of components required for the FIG. 15 circuit are generallyknown and have been elsewhere indicated. Therefore, since FIG. 16represents a more detailed description of FIG. 15, it is believed thoseskilled in the art will readily understand the circuitry and operationdepicted in FIG. 15 after reading the description to follow.

The description now turns to a description of FIG. 16 which constitutesa logic flow chart suited to the application related to FIGS. 12-15 and17. Since the components in FIG. 16 are identified and are known tothose skilled in the art and their relation in the circuit is shown, thedescription will next concern itself pri-' marily with the operation ofthe circuitry of FIG. 16. The Possible QRS-Complex Detector with outputat (a) detects the beginning and end of all possible" QRS-complexes. Thestart of a possible QRS complex is detected by the Possible QRS-ComplexStart Detector with output at (b) and the end of a possible QRS- Complexis detected by the Possible QRS-Complex End Detector with output at (d).The decision of whether the possible QRS-complex that is detected is atrue QRS-complex is made by the True QRS-Complex Detector with output at(c). The outputs at (c) and (d) are then combined through an And Gatewith output at (e). This output (e) represents the end of a trueQRS-complex The QRS-complex is analysed in two different ways: (1)Measurement of the time period of the QRS-complex; and (2) Measurementof the time period between two consecutive QRS-complex, i.e., R-Rinterval.

The measurement of the time period of the QRS- complex is accomplishedthrough the Percent Control-Time Classifier. The signal at (b) is thesignal to reset and then start this classifier which classifies the timeperiod of QRS-complex into one of five time intervals: (I) 110% or lessof control time, (11) 110% to 120% of control time, (III) 120% to 130%of control time, (IV) 130% to 150% of control time, or (V) 150% orgreater of control time. The control time is the time period of a normalQRS-complex for the given patient. The signal (f) occurs at the end of atrue QRS-Complex once every 256 times an hour. The pulse at (f) is thesignal to add to the Accumulating Counter For QRS Time Period. Dependingon the percent of control time classification of the QRS-complex, thiscounter is incremented by 0, 1, 2, 4, 8, or 16 counts. Eachclassification adds a set number to the counter. Classification (V) hasthe additional option of having its count value changed to 4, 8, or 16through Memory Latch Control 1. This memory latch control can be setthrough the previously mentioned externally accessible rotary switch252, not shown in FIG. 16 but shown in FIGS. 12 and 13. If the count onthe Accumulating Counter for QRS Time Period exceeds 256 in an hour thenthe output at (g) is a logic 1 otherwise (g) is a logic The measurementof the R-R interval is accomplished by the R-R Pulse Generator whichselects two consecutive true QRS-complexes once every 256 times an hourand outputs a logic 1 pulse at h equal in length to the time periodbetween the end pulses of these consecutive true end pulses. This pulseat (h) is then gated through an And Gate with a 1000 Hz. clock and theresulting pulses at (i) represent the number of 1000 Hz. pulses occuringduring a R-R interval once every 256 times an hour. These pulses at (i)are accumulated by the R-R Interval Counter with output at (i). At theend of each hour the contents of the RR Interval Counter is comparedwith the RR Control Value. This control value represents the number of1000 Hz. pulses that occur during a time period that is 20% less than anormal R--R interval for a given patient (i.e., a time periodcorresponding to a R-R frequency 20% faster than normal.) This controlvalue is set through the previously mentioned externally accessiblerotary switch 252 into Memory Latch control 2. If the hourly count isgreater than the control value then the present Day R-R Status (which isnormally a logic 1) is set to a logic 0. Once set to logic 0, it remainsat logic 0 for the remaining portion of the present day. At the end ofthe 24th hour this value is stored in the previous Day R-R Status foruse in making the present days pump decisions at the beginning of hours1, 9, and 17. This output at (k) is a logic 0 if any hourly R intervalcount for the previous 24-hour day was greater than the R--R ControlValue for a given patient (i.e., if the average R-R frequency during any18 hour of the 24 hour day was slower than the 20% greater than normalcontrol value). I

The two outputs at (g) and (k) control the pump operation. Normaloperation causes the pump to dispense at all even hours (Condition I inthe FIG. 17 Chart). Increase in frequency for the lowest hour frequencyfor the 24 hour period of the previous day (indicating need for moremedication), a logic 1 at (k), provides for the pump to dispenseadditional doses at hours 1, 9, and 17 (Condition II in the FIG. 17chart). These two operations occur in the following manner: If eitherthe output at (n) or (q) is a logic 1 then the input to the Pump Controlis a logic 1 at (r). A logic 1 pulse at (r) is the signal to turn on thepump. This signal at (r) is a logic 1 at even hours (output (m)normally, and at hours 1, 9, and 17 (output (p) under Condition II ofthe FIG. 17 Chart unless these conditions are altered by one of thefollowing restraints: If the output at (g) is a logic 1 for any hourthen the output of the 2 Hour Memory at (l) is set to a logic 0 for thenext 2 hours (normally this output at (l) is a logic 1 This signal l) isgated with the even hour pulse at (m) through an And Gate with output at(n). If the output at (g) is a logic 1 for any hour then the output ofthe 8 Hour Memory at (0) is set to a logic 0 for 8 hours. (Normally thisoutput at (0) is a logic 1.) This output (0) is gated with the logic 1pulse at hours 1, 9, and 17 at (p) and the pulse at (k) through an AndGate with output at (q)- With the foregoing in mind, it should be notedthat the power unit 210 of FIGS. l2l3 and which is associated with theFIGS. 15-16 circuitry, is appropriately geared to operate on a fiftyminute hour in contrast to the 60 minute hour for the logic circuit.This allows 10 minutes between the end of the power unit hour and theend of the logic system hour which allows for any margin of timing errorin the power unit movement due to increased work load.

In summary, there has been described an implantable system and methodspecifically useful for treating the human and animal body in a uniqueway. The power source may take many forms. It may be in the micropowerform referred to in my prior US. Pat. No. 3,692,027 or in otherequivalent miniaturized forms providing a long life, i.e., measured atleast in terms of days and preferably years, source of electricalenergy, for energizing the system electronics and for providing powerfor the drive member used to actuate the dispensing mechanism. Theapparatus lends itself to a wide variety of applications and themedication may include pharmacologically active drugs needed, bodyconstituents, energy compounds, radioactive materials, and the like.

It should also be noted that the term body and animal body as used inthe claims are intended to include animal, human and other livingbodies. Further, the term body is intended to encompass anyenvironmental body, whether living or otherwise adapted to receiving aself, micro powered and timed device for incremental dispensing ofsubstances into such body.

What is claimed is:

1. A self-contained and powered apparatus adapted to be totallyimplanted within a selected animal body, including human, forperiodically evaluating selected internal physiological states of suchbody and for periodically dispensing selected medication thereinaccording to such states while leaving the body ambulatory at all times,comprising:

a. a unitary housing adapted to be completely implanted and securedwithin and to the body at a selected site and having therein variouscompartments enclosed by said housing and adapted for mounting amedication storage member, a micro size power source, miniaturizeddriving and dispensing means adapted to being powered by such source fordispensing medication from such storage member, miniaturized electricaldata evaluation and timing circuit means adapted to being powered bysuch source and to processing physiological data including data obtainedfrom sensor means external of the housing to control the operation ofsaid driving and dispensing means and said housing being further adaptedto receive connections from external sensor means through the wall ofthe housing;

b. a storage member mounted within the implanted housing and adapted tostore selected medication to be dispensed in selected quantities;

c. a micro size power source mounted within the implanted housing andsecured proximate said storage member and having a useful working lifein terms of at least several days;

d. miniaturized electro-mechanical driving means mounted within theimplanted housing and adapted for being connected to and powered by saidsource;

e. miniaturized dispensing means mounted within the implanted housingand connected to receive said medication from said storage member andadapted to be powered by said driving means at selected times and beingadapted when so powered to withdraw from said storage member successivemeasured quantities of selected said medication and to discharge suchmedication from the implanted housing into said body;

f. sensing means selectively placed within said body externally of theimplanted housing and adapted to produce sensed signals convertible toelectrical data corresponding to a sensed condition within said body;

g. connector means connected to said sensing means and passing throughthe wall of said housing and adapted to transfer such signals to thehousing to be processed therein;

h. miniaturized electrical data evaluation and timing means mountedwithin the implanted housing and connected to be energized by said powersource and comprising:

1. miniaturized electrical circuit means connected through saidconnector means to said sensing means and adapted to receive selecteddata from said sensing means and convert such data into an electricallyprocessable form and adapted for electrically evaluating such senseddata at selected times; and

2. timing means operatively connected to said circuit means andproviding electrical time base information thereto whereby said drivingmeans is energized and actuates said dispensing means in coordinationwith selected evaluations.

2. The method utilizing the apparatus of claim 1 of periodicallyevaluating selected internal physiological states of an animal body,including human, and of periodically dispensing medication thereinaccording to such needs while leaving the body ambulatory at all times,comprising the steps:

20 a. implanting the housing of said apparatus in the body at a selectedsite and with a store of selected medication; b. implanting the sensingmeans of said appparatus at a selected site external of said housing andwithin the same said body and with said sensing means being connectedthrough the said connector means to the said circuit means of the saidapparatus; and

c. allowing said sensing means to operate, to produce signalscorresponding to physiological states within the said body and allowingsaid medication to be dispensed to a selected site within the body on aschedule determined by said data evaluation and timing means over a longperiod of time.

3. An apparatus as claimed in claim 1 including catheter means placedwithin the body externally of the implanted housing connected to receiveand transfer the medication discharged by said dispensing means to aselected treated site.

4. An apparatus as claimed in claim 1 wherein said drive meansconstitutes a solenoid having an armature and said dispensing meansconstitutes a solenoid armature operated dispenser.

5. An apparatus as claimed in claim 1 wherein said dispensing meansincludes a reciprocable bellows for receiving internally thereof,measuring and discharging said medication.

6. An apparatus as claimed in claim 1 wherein said storage member,dispensing means, sensing means and data evaluation and timing means areadapted for selectively dispensing plural sources of medication.

7. An apparatus as claimed in claim 1 wherein said drive meansconstitutes an electrical motor having a cam and said dispensing meansconstitutes a cam operated dispensing means.

8. An apparatus as claimed in claim 1 wherein said storage member,sensing means, dispensing means and evaluation and timing meansareadapted to storing, sensing the need for and dispensing doses of pluralmedications.

9. An apparatus as claimed in claim 8 wherein said dispensing means isadapted to dispensing said doses of plural medications to separate siteswithin said body.

10. An apparatus as claimed in claim 8 wherein said dispensing isaccording to plural sensing schedules.

11. An apparatus as claimed in claim 1 including externally availableportal means adapted for replenishing medication in said storage member.

12. An apparatus as claimed in claim 1 where said sensing means isadapted to sense and develop electrical signals corresponding to pluralmedical factors and said data evaluation and timing means is adapted toelectrically evaluate said factors and dispense said medicationaccording to such evaluation.

13. An apparatus as claimed in claim 1 wherein said sensing means sensespressure within said body.

14. An apparatus as claimed in claim 1 wherein said sensing means sensesan electrical activity in said body.

15. An apparatus as claimed in claim 1 wherein said sensing means sensesa chemical activity in said body.

16. In an apparatus as claimed in claim 1 wherein' said storage memberstores a single medication, said dispensing means comprises pluraldispensing means connected to a common said storage member and said dataand evaluation timing means is adapted to evaluate the need for and toseparately operate each said dispensing means to cause said medicationto be dis- 21 pensed independently through one or the other of saiddispensing means.

17. In an apparatus as in claim 1 wherein said storage member, sensingmeans, dispensing means, data evaluation and housing means are adaptedto sense the need for and to dispense a first medication on a regulartimed basis and a second medication on a special basis.

18. An apparatus as claimed in claim 1 wherein said dispensing meansincludes a discharge port and externally accessible portal meansenabling the entry of a suitable tool to clean said discharge port.

19. An apparatus as claimed in claim 1 wherein said storage member,sensing means, dispensing means and evaluation and timing means areadapted to dispensing medication in a wide range of combinations ofsingle or plural doses, single or plural medications, single or pluralsensed conditions, single or plural sites, and under single or pluraltiming schedules.

20. An apparatus as claimed in claim 1 adapted to dispense medicationfor prevention of recurrent tachycardias and arrythmias and wherein saidsensing means comprise a cardiac type sensor and said data evaluationand timing means includes an amplifying circuit connected to saidsensing means, a first QRS detector circuit connected to said amplifier,a second QRS period analysis and control value comparison circuitconnected to said first QRS detector circuit, an RR interval analysisand control value comparison circuit connected to said first QRSdetector circuit and said QRS period analysis circuit, an evaluatinglogic circuitry connected to said second QRS period analysis and said RRinterval analysis circuit, a timing circuit connected to time saidsecond QRS period circuit, said RR interval analysis circuit and saidlogic evaluation circuit and wherein said dispensing means is controlledby said logic evaluation circuit.

1. A self-contained and powered apparatus adapted to be totallyimplanted within a selected animal body, including human, forperiodically evaluating selected internal physiological states of suchbody and for periodically dispensing selected medication thereinaccording to such states while leaving the body ambulatory at all times,comprising: a. a unitary housing adapted to be completely implanted andsecured within and to the body at a selected site and having thereinvarious compartments enclosed by said housing and adapted for mounting amedication storage member, a micro size power source, miniaturizeddriving and dispensing means adapted to being powered by such source fordispensing medication from such storage member, miniaturized electricaldata evaluation and timing circuit means adapted to being powered bysuch source and to processing physiological data including data obtainedfrom sensor means external of the housing to control the operation ofsaid driving and dispensing means and said housing being further adaptedto receive connections from external sensor means through the wall ofthe housing; b. a storage member mounted within the implanted housingand adapted to store selected medication to be dispensed in selectedquantities; c. a micro size power source mounted within the implantedhousing and secured proximate said storage member and having a usefulworking life in terms of at least several days; d. miniaturizedelectro-mechanical driving means mounted within the implanted housingand adapted for being connected to and powered by said source; e.miniaturized dispensing means mounted within the implanted housing andconnected to receive said medication from Said storage member andadapted to be powered by said driving means at selected times and beingadapted when so powered to withdraw from said storage member successivemeasured quantities of selected said medication and to discharge suchmedication from the implanted housing into said body; f. sensing meansselectively placed within said body externally of the implanted housingand adapted to produce sensed signals convertible to electrical datacorresponding to a sensed condition within said body; g. connector meansconnected to said sensing means and passing through the wall of saidhousing and adapted to transfer such signals to the housing to beprocessed therein; h. miniaturized electrical data evaluation and timingmeans mounted within the implanted housing and connected to be energizedby said power source and comprising:
 1. miniaturized electrical circuitmeans connected through said connector means to said sensing means andadapted to receive selected data from said sensing means and convertsuch data into an electrically processable form and adapted forelectrically evaluating such sensed data at selected times; and 2.timing means operatively connected to said circuit means and providingelectrical time base information thereto whereby said driving means isenergized and actuates said dispensing means in coordination withselected evaluations.
 2. timing means operatively connected to saidcircuit means and providing electrical time base information theretowhereby said driving means is energized and actuates said dispensingmeans in coordination with selected evaluations.
 2. The method utilizingthe apparatus of claim 1 of periodically evaluating selected internalphysiological states of an animal body, including human, and ofperiodically dispensing medication therein according to such needs whileleaving the body ambulatory at all times, comprising the steps: a.implanting the housing of said apparatus in the body at a selected siteand with a store of selected medication; b. implanting the sensing meansof said appparatus at a selected site external of said housing andwithin the same said body and with said sensing means being connectedthrough the said connector means to the said circuit means of the saidapparatus; and c. allowing said sensing means to operate, to producesignals corresponding to physiological states within the said body andallowing said medication to be dispensed to a selected site within thebody on a schedule determined by said data evaluation and timing meansover a long period of time.
 3. An apparatus as claimed in claim 1including catheter means placed within the body externally of theimplanted housing connected to receive and transfer the medicationdischarged by said dispensing means to a selected treated site.
 4. Anapparatus as claimed in claim 1 wherein said drive means constitutes asolenoid having an armature and said dispensing means constitutes asolenoid armature operated dispenser.
 5. An apparatus as claimed inclaim 1 wherein said dispensing means includes a reciprocable bellowsfor receiving internally thereof, measuring and discharging saidmedication.
 6. An apparatus as claimed in claim 1 wherein said storagemember, dispensing means, sensing means and data evaluation and timingmeans are adapted for selectively dispensing plural sources ofmedication.
 7. An apparatus as claimed in claim 1 wherein said drivemeans constitutes an electrical motor having a cam and said dispensingmeans constitutes a cam operated dispensing means.
 8. An apparatus asclaimed in claim 1 wherein said storage member, sensing means,dispensing means and evaluation and timing meansare adapted to storing,sensing the need for and dispensing doses of plural medications.
 9. Anapparatus as claimed in claim 8 wherein said dispensing means is adaptedto dispensing said doses of plural medications to separate sites withinsaid body.
 10. An apparatus as claimed in claim 8 wherein saiddispensing is according to plural sensing schedules.
 11. An apparatus asclaimed in claim 1 including externally available portal means adaptedfor replenishing medication in said storage member.
 12. An apparatus Asclaimed in claim 1 where said sensing means is adapted to sense anddevelop electrical signals corresponding to plural medical factors andsaid data evaluation and timing means is adapted to electricallyevaluate said factors and dispense said medication according to suchevaluation.
 13. An apparatus as claimed in claim 1 wherein said sensingmeans senses pressure within said body.
 14. An apparatus as claimed inclaim 1 wherein said sensing means senses an electrical activity in saidbody.
 15. An apparatus as claimed in claim 1 wherein said sensing meanssenses a chemical activity in said body.
 16. In an apparatus as claimedin claim 1 wherein said storage member stores a single medication, saiddispensing means comprises plural dispensing means connected to a commonsaid storage member and said data and evaluation timing means is adaptedto evaluate the need for and to separately operate each said dispensingmeans to cause said medication to be dispensed independently through oneor the other of said dispensing means.
 17. In an apparatus as in claim 1wherein said storage member, sensing means, dispensing means, dataevaluation and housing means are adapted to sense the need for and todispense a first medication on a regular timed basis and a secondmedication on a special basis.
 18. An apparatus as claimed in claim 1wherein said dispensing means includes a discharge port and externallyaccessible portal means enabling the entry of a suitable tool to cleansaid discharge port.
 19. An apparatus as claimed in claim 1 wherein saidstorage member, sensing means, dispensing means and evaluation andtiming means are adapted to dispensing medication in a wide range ofcombinations of single or plural doses, single or plural medications,single or plural sensed conditions, single or plural sites, and undersingle or plural timing schedules.
 20. An apparatus as claimed in claim1 adapted to dispense medication for prevention of recurrenttachycardias and arrythmias and wherein said sensing means comprise acardiac type sensor and said data evaluation and timing means includesan amplifying circuit connected to said sensing means, a first QRSdetector circuit connected to said amplifier, a second QRS periodanalysis and control value comparison circuit connected to said firstQRS detector circuit, an R-R interval analysis and control valuecomparison circuit connected to said first QRS detector circuit and saidQRS period analysis circuit, an evaluating logic circuitry connected tosaid second QRS period analysis and said R-R interval analysis circuit,a timing circuit connected to time said second QRS period circuit, saidR-R interval analysis circuit and said logic evaluation circuit andwherein said dispensing means is controlled by said logic evaluationcircuit.